Because of the reported harmful effects of tobacco smoking and also due to the current social attitudes to smoking, resulting in ever-increasing smoke-free public areas, there is great pressure on tobacco smokers to stop smoking or to find a more socially acceptable alternative.
For those who are unable to give up smoking completely, various forms of nicotine-replacement therapy have been suggested.
Nicotine-containing chewing gum is available commercially and has provided a satisfactory substitute for tobacco-smoking for some people. For many people, nicotine gum does not alleviate the craving for tobacco, due to the gradually achieved and low blood nicotine levels produced. Many people also experience unpleasant side effects, such as nausea and indigestion (Jarvis et al., British Medical Journal, Vol. 285, p. 537 (1982); Schneider, Comprehensive Therapy, Vol. 13, p. 32 (1987)).
Nicotine-containing nose drops have been reported (Russel et al., British Medical Journal, Vol. 286, p. 683 (1983); Jarvis et al., Brit. J. of Addiction, Vol. 82, p. 983 (1987)). Nose drops, however, are difficult to administer and are not convenient for use at work or in other public situations. There may also be local nasal irritation with use of nicotine nose drops. The difficulty in administration also results in unpredictability of the dose of nicotine administered.
The use of skin patches for transdermal administration of nicotine has been reported (Rose, in Pharmacologic Treatment of Tobacco Dependence, (1986) pp. 158-166, Harvard Univ. Press). Nicotine-containing skin patches can cause local irritation and the absorption of nicotine is slow and affected by cutaneous blood flow.
U.S. Pat. Nos. 4,920,989 and 4,953,572 disclose the use of an inhaled nicotine aerosol, sometimes in conjunction with nicotine skin patches, as a means of reducing tobacco smoking. When skin patches were used, transdermal absorption of nicotine gave blood nicotine levels comparable to those achieved by tobacco smoking. The use of the nicotine aerosol alone delivered substantially less nicotine to the blood than is seen while smoking tobacco but did provide sensations of irritation in the airways of the user, thus mimicking sensations associated with tobacco smoking.
In order to ensure that the droplets of nicotine solution would be carried into the respiratory airways on inhalation through the mouth in imitation of smoking, rather than being deposited in the oral cavity, the aerosol droplet size employed was 10 microns or less.
Although a certain degree of airway irritation is desired to mimic smoking, this cannot be readily controlled and the irritation may be pronounced, making the use of a nicotine aerosol undesirable.
Perkins et al. (Behavior, Research Methods, Instruments and Computers (1986), vol. 18, p.420 and Psychopharm. (1989), vol. 97, p. 529) reported use of a nicotine aerosol spray as a means of administering nicotine to a test subject in controllable amounts in order to study the physiological effects of nicotine. Under their test conditions, they were able to employ a dilute solution of nicotine administered in several doses to deliver 1.8 ml. over a 5 minute period to resting subjects and did not investigate a practical nicotine preparation for everyday use, such as is required for anti-smoking treatment or as a substitute for tobacco smoking.
U.S. Pat. No. 4,579,858 discloses a nicotine-containing preparation of high viscosity which is administered to the nose as a viscous plug. The surface area of such a plug which is in contact with the nasal mucosa is limited and this is reflected in the relatively low blood nicotine levels achieved by this method of nicotine administration.
There remains a need for a nicotine preparation suitable as a substitute for tobacco smoking, which can be conveniently used in public, as the subject goes about his or her normal activities over an extended period of time.